Pregnancy is a period that places great physiological stress on both the mother and the fetus. When pregnancy is compounded by endocrine disorders such as hypothyroidism, the potential for maternal and fetal adverse outcomes can be immense. While a lot of attention has been focused on the adverse fetal outcomes consequent to hypothyroidism, attention is also being gradually directed towards the adverse maternal outcomes of this disorder. Role of antibody positivity in influencing outcomes in a euthyroid woman, also needs further clarification. Prompt diagnosis and treatment of hypothyroidism in pregnancy is very essential. Subclinical hypothyroidism also needs to be detected and treated to prevent adverse outcomes, especially maternal. Since women with hypothyroidism during pregnancy, especially of the autoimmune variety might have a flare up of the disorder post-partum, or might continue to require thyroxine replacement post-partum, adequate follow-up is mandatory. While targeted case finding is generally practised, recent evidence seems to indicate that universal screening might be a better option. In conclusion, routine screening, early confirmation of diagnosis and prompt treatment. Allied with regular post-partum follow up, is required to ensure favourable maternal and fetal outcomes. Thyroid physiology is perceptibly modified during normal pregnancy. These alterations take place throughout gestation, help to prepare the maternal thyroid gland to cope with the metabolic demands of pregnancy, are reversible post-partum and the interpretation of these changes can pose a challenge to the treating physician.

1. HYPOTHYROISM IN
PREGNANCY
DR ALKA MUKHERJEE NAGPUR MS
MBBS DGO FICOG FICMCH PGDCR PGDMLS MA(PSY)

2. ANATOMY
2
A Small Butterfly Shaped ENDOCRINE Gland At The Base Of
The Neck, Against C5, C6, C7 & T1.
Consist Of Right & Left Lobe Joined By Isthmus, A 3rd
Pyramidal Lobe Might Project Upwards From Isthmus
Capsules – 2 – True & False
Larger In Females Than Males
Development – Ectoderm Of The Floor Of Primitive Oral
Cavity

3. HISTOLOGY OF THE THYROID GLAND
Thyroid gland contains
numerous follicles,
composed of follicle
cells and colloid.
Maintenance of normal metabolic
activity-continuous production of
thyroid hormone at right
concentration
Coordinated interaction between
Hypothalamus, Pituitary & Thyroid.
CLASSIC EXAMPLE-ENDOCRINE
FEEDBACK MECHANISM

4. FUNCTIONS OF THYROID GLAND
Major function-
absorption of
iodine
Synthesis &
secretion of two
important
hormones,T3&T4
-Metabolic
Homeostasis Of
The Body
Parafollicular cells
of thyroid gland-
CALCITONIN
-CALCIUM
HOMEOSTASIS OF
BODY
T4 –major thyrois
hormone,thyroid
gland produces
100%
Half life of T4 -7
days
4

5. THYROID HORMONES
Two hormones are
secreted by Thyroid
gland
1.
Tetraiodothyronine
(T4) usually called
Thyroxine
2. Triiodothyronine
(T3)
Thyroid secretes 80
mcg of T4,
but only 5 mcg of
T3/day.
Derived from an
amino acid
(tyrosine)
Thyroid hormones
are made from
Tyrosine and Iodine

6. MATERNAL THYROID PHYSIOLOGY
• During pregnancy, maternal thyroid function is modulated by three
factors.
• An increase in HCG concentration that stimulate the thyroid glands,
• Significant increases in urinary iodide excretion resulting in a fall in
plasma iodine concentration
• An increase in thyroxine – binding globulin (TBG) DURING The first
trimester , resulting in increased binding of thyroxine
• Total T3 & T4 are increased, but Free T4 & Free T3 remain normal & patient remains
euthyroid.
• Increased T4 & T3 in early pregnancy help to maintain the hyper metabolic state
• Sometimes, estimation of TSH during pregnancy is erroneous due to interference by
HCG .
• Therefore during pregnancy, it is always advisable to get FT3 & FT4 done rather than
Total T4 & T3.

7. TBG
Urinary Iodine
Excretion
BMR
Beta HCG
MATERNAL THYROID PHYSIOLOGY

8. HCG & THYROID PHYSIOLOGY IN PREGNANCY
8
Human chorionic gonadotropin (HCG), secreted by the placenta, also
impacts thyroid function because it simulates thyroid‐stimulating hormone
(TSH) activity in vivo, thereby suppressing its secretion.
The structure of HCG is similar to TSH. HCG mimics & acts like TSH.
Throughout pregnancy, TSH values are lower than in the pre‐pregnant state,
and may even be below the classical lower limit of 0.4 miu/L.
Since the levels of HCG decrease as the pregnancy increases, the levels of
TSH follow the reverse trend.
Serum hCG has intrinsic thyrotropic activity, which increases after fertilization
and peaks at 10 to 12 weeks.
Hence, in the first trimester , free T3 and T4 levels increase slightly and TSH
levels decrease in the first trimester with a readjustment in the second and
third trimesters, when hCG levels decrease.
As a consequence, cut-offs to determine hypothyroidism in pregnancy are
different in the first trimester and the rest of the pregnancy.

9. EFFECT OF HCG
• Pregnancy results in number
of important physiological &
hormonal changes that alter
thyroid function due to
influence of two main
hormones.
• 1. HCG
• 2. Estrogen
• Baby remains dependent on
mother for ingestion of
adequate amount of iodine
which is essential for
synthesis of thyroid
hormones

10. The most notable change is the increase in thyroxine-binding globulin
(TBG).
This begins early in the first trimester, plateaus during midgestation,
and persists until shortly after delivery.
This is due to stimulation of TBG synthesis by elevated maternal
estrogen levels, and more importantly, due to a reduced hepatic
clearance of TBG because of estrogen-induced sialylation.
This increased TBG concentration leads to an expansion of the extra-
thyroidal pool and results in elevated total T3 and T4 levels due to an
increase in maternal thyroid hormone synthesis.
Maternal thyroid hormone synthesis is also increased due to an
accelerated renal clearance of iodide resulting from the increased
maternal glomerular filtration rate.
TBG & MATERNAL THYROID PHYSIOLOGY

11. PLACENTAL DEIODINASES & MATERNAL THYROID
PHYSIOLOGY
Enhanced metabolism of T4 in the second and third
trimesters, due to a rise in placental type II and type III
deiodinases, which convert T4 to T3 and T4 to reverse T3
and T2 respectively, act as further impetus to T4 synthesis.
Plasma iodide levels decrease due to both increased
thyroxine metabolism and increased renal iodide
clearance.
All these changes lead to an increase in the size of the
thyroid gland in 15% of pregnant women, which returns to
normal in the post-partum period.

12. PHYSIOLOGY OF THE FETAL THYROID
• Fetal thyroid gland develops as an out pouching in midline of the anterior
pharyngeal floor, migrates caudally, to reach its final position by 7 weeks of
gestation.
• Fetal thyroid is capable of trapping iodine by 12 weeks and can synthesize
thyroxine by 14 weeks of gestation.
• However, significant hormone secretion is not seen till 18–20 weeks of
gestation. Thereafter, fetal TSH, T4, and TBG gradually rise to adult levels by
36 weeks gestation.
• But T3 and free T3 levels do not rise to adult levels , as placental type III
deiodinase converts most fetal T4 to reverse T3; the fetal brain which has
elevated levels of type II deiodinase, is an exception.
• TSH transfer across placenta is not significant, but T3 and T4 transport can
be considerable. This is of special relevance in congenital hypothyroidism,
where studies have shown that umbilical cord T4 levels in neonates with
congenital hypothyroidism can be up to 50% of the normal.
• This transferred T4 can play a crucial role in near normal fetal cognitive
development in congenital hypothyroidism. Transplacental transfer of TRH,
iodine, anti-thyroid drugs and thyroid stimulatory immunoglobulin (TSI)
also occurs

13. THYROID PHYSIOLOGY IN PREGNANCY
Pregnancy is Iodide-Deficient state
 BMR by 15-20%
 Iodine clearance due to increased GFR (upto 50%) &
reduced tubular re-absorption
Hence requirement of Thyroxin & Iodine In Pregnancy.
Iodine Requirement:
Non-pregnant Females 150 microg/day
Pregnancy &
Breastfeeding
200-250 microg/day

14. THYROID PHYSIOLOGY IN PREGNANCY
Estrogen stimulates TBG production from liver.
Normally T3 & T4 occur in two forms:
 Bound with TBG
 Free(Active)
On account of increased TBG, Bound form increases.

15. PREGNANCY IS A STRESS TEST FOR THE THYROID,
Pregnancy impacts the
functioning of the thyroid
gland profoundly and is
associated with
a 10%–40% increase in the
size of the gland
(iodine‐replete areas show
greater increase),
a 50% increase in the
production of thyroxine
(T4) and triiodothyronine
(T3), and
a 50% increase in the daily
requirement of iodine.
These physiological changes -
pregnant, iodine‐deficient, euthyroid
woman in the first trimester
hypothyroid during the later stages
of pregnancy and postpartum
thyroiditis in women with underlying
Hashimoto's disease who were
euthyroid prior to conception.
Ten percent to 20% of all
pregnant women in the
first trimester of
pregnancy are thyroid
peroxidase (TPO) or
thyroglobulin (Tg)
antibody positive and
euthyroid.
Sixteen percent of the
women who are euthyroid
and positive for TPO or Tg
antibody in the first
trimester will develop a
TSH that exceeds 4.0
mIU/L by the third
trimester, and

16. EPIDEMIOLOGY OF THYROID DISEASE
• 1.8% of world total population.
• Second only to DM as most
common endocrine disorder.
• Incidence increases with age.
• More common in females.
• 2-3% of older women.
• 42 million people in India suffer
from thyroid disease
•5 common thyroid diseases in
India.
•Hypothyroidism(Highest)
•Hyperthyroidism
•Goitre and Iodine Deficiency
disorders
•Hashimotos’s thyroiditis
•Thyroid Cancer
1. [Last accessed on 2011 April 2]. Available from:http://www.ias.ac.in/currsci/oct252000/n%20kochupillai.PDF .
2. Desai PM. Disorders of the Thyroid Gland in India. Indian J Pediatr. 1997;64:11–20. [PubMed]
3. Usha Menon V, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V, Kumar H. High prevalence of undetected thyroid disorders in an iodine
sufficient adult south Indian population. J Indian Med Assoc. 2009;107:72–7. [PubMed]
Over 40 Million Indians suffer from
Thyroid disorders of which
Hypothyroidism is a major concern.

17. Hypothyroidism is difficult to be diagnosed during pregnancy as the signs can
belong to pregnancy itself.
Changes in thyroid function have a major negative impact on both mother and
fetus.
Thyroid pathology worsens
during pregnancy.
Hypothyroidism can be pre-
existent or may begin
during pregnancy period.
Most of the patients who
presented hypothyroidism
during pregnancy have a
history of thyroid disease
for which they have
undergone treatment
(medical, surgical or
radioisotopes).
Complications that arise
depend on the severity of
hypothyroidism, on how
appropriately and early the
treatment will be initiated,
on other obstetrical and
extragenital pathologies
associated with the present
pregnancy.
Clinical symptoms –
polymorphic & nonspecific,
and are related mainly to
the time of occurrence and
to the severity of thyroid
hormone deficiency.
The appropriate, early
administered treatment and
maintenance of a normal
level of thyroid hormones
minimize the risk of
maternal and fetal
complications and make it
possible that the pregnancy
may be carried to term
without severe
complications.

18. HORMONAL CHANGES AND METABOLIC NEEDS
DURING PREGNANCY
• Result in profound alterations of biochemical and clinical
parameters which characterize the thyroid gland, changes that
express themselves through a state of thyroid hyperstimulation
and a relative hypothyroxinemy or a subclinic hypothyroidism.
• When pregnancy overlaps maternal endocrine imbalance,
undesirable consequences for both mother and fetus may appear.
• Associated with an increased risk of abortion, habitual abortion,
premature delivery, intrauterine fetal death, fetal retardation and
fetal congenital anomalies, congenital hypothyroidism, postpartum
bleeding, anemia, post-partum depression and cardiac
dysfunction, which leads to increased maternal morbidity,
perinatal morbidity and mortality

19. 19
Hypothyroidism common in pregnancy.
Two types –
.Overt hypothyroidism – defined as increased serum TSH [> 10 miu/ l]
associated with decreased concentration of thyroxine as a result of
negative feedback
.Subclinical hypothyroidism –increase in serum TSH [ 4-10 m iu/ l] with
normal concentration of thyroxine & triidothyronine.
Incidence – overt-0.2 – 2.5
- Subclinical- 5- 20 %
- Thyroid antibodies > 60 % females in reproductive age grp

20. WHAT HYPOTHYROIDISM?
• Under-activity of the thyroid
• Decreased secretion of thyroid hormones
• Deficiency of T3 and T4
 Clinical manifestations due to deficiency of
thyroid hormones
 Clinical manifestation depends on
Age of the patient
The cause of the disorder
Primary Hypothyroidism-
Caused by damage to the thyroid gland
Secondary Hypothyroidism-
Caused by damage to the pituitary gland &
therefore low production of Thyroid Stimulating
Hormone (TSH)
Tertiary Hypothyroidism-
Caused by the failure of the hypothalamus to release
Thyrotropin-releasing hormone (TRH)

21. PREVALENCE OF MATERNAL HYPOTHYROIDISM
• Maternal Hypothyroidism is much
more common than generally
acknowledged.
• The recent data shows alarmingly
high prevalence of the maternal
hypothyroidism both in India as well
as in USA.

22. • Autoimmune hypothyroidism:
- Hashimoto’s thyroiditis;
Atrophic thyroiditis
• Iatrogenic:
- Radio-iodine therapy;
Thyroidectomy
- External radiation to the neck
(lymphoma/CA)
• Drugs :
- Antithyroid drugs,
amiodarone, lithium,
interferon
• Congenital hypothyroidism:
- Thyroid agenesis;
Dyshormogenesis; TSH-R
mutation
• Iodine deficiency
• Infiltrative disorder
PRIMARY CAUSES
• Hypopituitarism (2°):
– Tumour
– Surgery
– Radiation
– Postpartum: Sheehan’s
syndrome
• Hypothalamic causes (3°):
– Tumour
– Trauma
• Peripheral resistance (rare)
2°, 3° CAUSES

23. ROLE OF THYROID
HORMONES:
• Essential for normal growth of tissues
• Stimulates basal metabolic rate.
• Increases intestinal glucose reabsorption & ATP production
• Development of the skeletal system & musculature.
• Essential for normal brain development & regulates
synaptogenesis, neuronal integration, myelination
• Deficiency lead to short stature & mental deficits

24. • Fatigue
• Increased sensitivity to
cold
• Constipation
• Dry skin
• Weight gain
• Puffy face
• Hoarseness
• Muscle weaknes
• Elevated blood cholesterol
level
• Muscle aches, tenderness
and stiffness
• Pain, stiffness or swelling in
your joints
• Heavier than normal or
irregular menstrual periods
• Thinning hair
• Slowed heart rate
• Depression
• Impaired memory
• Enlarged thyroid gland
(goiter)
HYPOTHYROIDISM: SIGNS AND SYMPTOMS

25. HYPOTHYROIDISM IN PREGNANCY
• Elevated serum TSH concentration
2.5% of pregnancies
• In iodine sufficent environment
- Hashimoto’s thyroiditis
- Prior radioactive iodine treatment
- Surgical ablation of Graves’
disesase
- Less common causes :
Overtreatment of hyperthyroidism
with thionamides , transient
hypothyroidism owing to
postpartum thyroditis ,
medications that alter the
absorption or metabolism of
levothyroxine , and pituitary
hypothalamic disease
25
• One of the most common endocrine
disorders in pregnancy1
• Most common cause: endemic iodine
deficiency2
• Women with hypothyroidism carry
an increased risk of infertility,
miscarriage, and obstetric
complications1
• Foetal complications: premature
birth, low-birth weight (LBW), fetal
distress in labor, fetal death,
perinatal death, and congenital
hypothyroidism1
• Even an untreated subclinical
hypothyroidism during pregnancy
can lead to cognitive impairment in
the offspring.3

26. 26

27. HYPOTHYROIDISM IN PREGNANCY RISKS
MATERNAL FOETAL
Anaemia & CHF Cognitive
impairment
Pre-eclampsia Neurological
abnormalities
Placental
Abnormalities
??
Developmental
abnormalities
Low Birth Weight
infants
Congenital
Hypothyroidism
Post Partum
Haemorrhage
Myopathy

28. COMPLICATIONS OF MATERNAL HYPOTHYROIDISM IF NOT
TREATED
Labor – diskinetic, longer due to the existence of the hypomyotonia and the simultaneous cardio-
breathing problems; hypokinesis
Anomalies of fetus cardiac rhytm (FCR) – fetal suffering: alterations of the basic cardiac rhythm
(tachycardia, bradicardia), of FCR variability (diminution until their loss or periodical variations of
FCR in relation with the uterus contractions, a type of belated slow-ups)
APGAR mark – frequently lower at pregnant women who continued to be hypothyroidic until the
due term
Vitiated pelvis (limit pelvis) which can be the reason of various cephalic-pelvis disproportions
Presentations that are close to distocia – pelvic presentation
Post-partum haemorrhages occur through uterus hypotony and through coagulation disorders
(problem of the plaque adhesiveness)
Post-partum depression, post-partum thyroiditis, hypogalactia

29. THE CAUSES OF THE HYPOTONY AND HYPO-
CONTRACTIONS IN HYPOTHYROIDISM
The causes of hypotony are
 the endogen intoxications,
 the change of muscular tissue,
 the myxedema impregnation,
 the hypovitaminosis (B1 vitamin),
affecting the transmission of the nervous
influx, affecting the endocrine
metabolism,
 water-electrolitic change which leads to
the change of the functional biometrical
schemes and to the change of the
interaction between actin and myosin:
a)the K and the intracellular Mg decrease due
to the metabolic acidosis and therefore the
contraction is more difficult, Ca decreases and
the equilibrium of P, bicarbonate and H ions is
disturbed;
B) the metabolic acidosis also modifies the
extracellular distribution of Na, Ca, Mg and K
and has a negative influence on the
contractions through the decrease of the
membrane potential, which leads to
insufficient contraction.
 Hypotonia, having a tonus less than
10 mmHg,
 Hypokinesis - Hypokinesis
(contractions which are rarer than
two within 10 minutes with the
contraction value of less then
25mmHg)
 Labour is slow or long, with
possibilities of interruption,
 real uterus inertia, which can be
primitive (ante-partum determined)
or secondary (intra-partum
determined).
 The insufficient labour - 35.2% at
the pregnant women, who
remained with hypothyroidism at
the end of pregnancy.

30. LOW APGAR score
APGAR score depends of the uterus-placenta circulation and the proper
oxygenation of the fetal-placenta complex during pregnancy and it is
frequently lower at pregnant women who continued to have
hypothyroidism until the due term.
In hypothyroidism, the cardiac debit is not adequate and the uterus-
placenta circulation becomes insufficient, which induces a moderate and
chronic fetal hypoxia, fetal bradycardia, fetal hypotrophy, diminution of
fetal moves and an insufficient tolerance of the delivery by the fetus.
The intrauterine chronic hypoxia of the newborn can be met in the
literature at variable percentages between 14%-22% at pregnant women
with hypothyroidism.
A series of studies, with recent reconfirmed results, showed that the
treatment with T4 can improve the obstetrical prognosis but it does not
modify the neurological development of the newborn on the long term,
the cognitive performances being changed;
the maternal hypothyroixinemia on early term pregnancies can have
irreversible negative effects on the newborn's state and placenta. Some
antioxidants (retinol, tocopherol etc.), are usually used in the treatment of
the fetal-placenta insufficiency.

31. VITIATED PELVIS (LIMIT PELVIS)
Intricate mechanisms (direct and
indirect effects of the thyroid
hormones) since the very beginning
of the pre-gestation period, which
can affect the pelvic bones (lower
bone density, even osteoporosis), of
the spine (multiple deformations),
problems of the articulations
through the specific infiltration,
various artropaties, inflammatory or
non-inflammatory, poliartritis,
artrosis.
Excessive deposits of mucous
polysaccharides and glucose in the
tissues, affecting protein synthesis,
diminution of the insulin level, as a
growth factor, can lead to various
muscles and skeleton symptoms.
A clear mechanism is not
established, but a decrease in the
proliferation of the cartilage cells
and bone tissue and
chondrocalcinosis

32. POST-PARTUM HEMORRHAGES IN HYPOTHYROIDISM
Are produced both through the uterus hypotony and coagulation problems,
with plaque adhesiveness problem.
Various studies (Leung, Buckshee, Davis) from the literature indicate a
percentage between 7% and 19%.
POST-PARTUM THYROIDITIS
The etiology of the post-partum thyroiditis has not been well-understood yet
but a problem in the self immunity can be probably caused by a constant
increase of the level of anti-microzomes antibody in the first trimester of the
pregnancy. Post-partum thyroiditis affects 2-7% of the pregnant women. The
hypothyroid phase follows a hyperthyroid phase and it manifests after 5-7
months in post-partum.

33. FUTURE SEQUALAE
The hypothyroid can
remain permanent (12-
61%) and euthyroiditis
appears in 5% of the
cases.
According to recent
studies, the incidence
has very wide limits,
between 1.1-2.1%,
within the first year
after delivery;
The presence of the thyroid
antibodies during the first
trimester of the pregnancy
determines an increase by
35% of the incidence and
the risk of developing a
post-partum thyroid is of
50%; if they are still
present in the third
trimester, the risk increases
by 80%; the relapse, with a
similar evolution and
intensity, usually appears
after future pregnancies.

34. POSTPARTUM DEPRESSION & PUERPERIAL PSYCHOSIS
IN HYPOTHYROIDISM
The level of hormone production by the placenta has a major role in the development of
psychological disequilibrium in puerperium.
The depression of pituitary function and the reduction of adrenaline and thyroid hormones
production may be included among the potential pathogenic factors;
low levels of progesterone or free tryptophan from the plasma,
the free usage of agents having vasoactive potential during intrapartum and postpartum and the
chronic lack of beta-endorphine along with the increase of the dopaminergic activity may be
responsible for these changes.
During post-partum, the adrenocorticotropic-hormone and the arginine-vasopressin are being
released, and carried through the portal circulation system until reaching the hypophysis where they
induce the production of ACTH, which reacts upon the corticoadrenal and releases cortisol.

35. COMPLICATIONS IN PREGNANCY, DELIVERY AND ON THE NEWBORN.
The increase of the preeclampsia incidence, of the premature delivery, of
the post-partum depressions and haemorrhages could be explained
through a maturation process of the placenta and they appear especially
if there is a severe hypothyroidism, but they have been also signalled in
the cases of subclinical hypothyroidism.
Complications in the pregnancies associated with hypothyroidism are
complex and serious, with an important increase of the maternal
morbidity, and perinatal morbidity and mortality. ❑

36. DISORDERS OF HYPOTHYROIDISM

37. INCREASED PREGNANCY LOSS RATE IN THYROID ANTIBODY
NEGATIVE WOMEN WITH TSH LEVELES BETWEEN 2.5 AND
5.0 THE FIRST TRIMESTER OF PREGNANCY
Evaluated 4123 Thyroid
TPO Ab negative pregnant women
with TSH =/< 5mlU/LA
TSH < 2.5mlU/L TSH 2.5-5.0mlU/L
Not given any treatment for TSH correction

38. RECOMMENDATIONS & TAKE HOME
• RECOMMENDATION 1 - Trimester-specific reference ranges
for TSH, as defined in populations with optimal iodine
intake, should be applied. Level B-USPSTF
• RECOMMENDATION 2 - If trimester-specific reference ranges
for TSH are not available in the laboratory, the following
reference ranges are recommended:
• first trimester, 0.1–2.5 mIU/L;
• second trimester, 0.2–3.0 mIU/L;
• third trimester, 0.3–3.0 mIU/L.
Level I-USPSTF

39. • RECOMMENDATION 3 - The optimal method to assess serum
FT4 during pregnancy is measurement of T4 in the dialysate or
ultrafiltrate of serum samples employing on-line
extraction/liquid chromatography/tandem mass
spectrometry (LC/MS/MS). Level A-USPSTF
• RECOMMENDATION 4 - If FT4 measurement by LC/MS/MS is
not available, clinicians should use whichever measure or
estimate of FT4 is available in their laboratory, being aware of
the limitations of each method. Serum TSH is a more accurate
indication of thyroid status in pregnancy than any of these
alternative methods. Level A-USPSTF
• RECOMMENDATION 5 - In view of the wide variation in the
results of FT4 assays, method-specific and trimester-specific
reference ranges of serum FT4 are required. Level B-USPSTF

40. • RECOMMENDATION 6 - OH should be treated in pregnancy.
This includes women with a TSH concentration above the
trimester-specific reference interval with a decreased FT4, and
all women with a TSH concentration above 10.0 mIU/L
irrespective of the level of FT4. Level A-USPSTF
• RECOMMENDATION 7 - Isolated hypothyroxinemia should not
be treated in pregnancy. Level C-USPSTF

41. : How is isolated hypothyroxinemia defined in
pregnancy?
• Isolated hypothyroxinemia is defined as a normal maternal TSH concentration in
conjunction with FT4 concentrations in the lower 5th or 10th percentile of the
reference range.
What adverse outcomes are associated with isolated hypothyroxinemia in
pregnancy?
It is debated whether isolated hypothyroxinemia causes any adverse effects on the
developing fetus. Pop and colleagues reported a decrease in psychomotor test
scores among offspring born to women with FT4 indices in the lowest 10th
percentile. These mothers often had normal serum TSH values.
Li et al. observed a similar reduction in the IQ of the offspring whose mothers
experienced either hypothyroidism or isolated hypothyroxinemia during the
first trimester.
Henrichs and colleagues recently published data from the Generation R study,
conducted in the Netherlands - prospective, nonrandomized investigation
evaluated communication development in children born to women with
isolated hypothyroxinemia. A 1.5- to 2-fold increased risk of adverse findings (at
3 years of age) was associated with maternal FT4 in the lower 5th and 10th
percentiles.

42. RECOMMENDATION 8 - SCH has been associated with adverse maternal
and fetal outcomes. However, due to the lack of randomized
controlled trials there is insufficient evidence to recommend for or
against universal LT4 treatment in TAb− pregnant women with
SCH. Level I-USPSTF
RECOMMENDATION 9 - Women who are positive for TPOAb and have
SCH should be treated with LT4. Level B-USPSTF
RECOMMENDATION 10 - The recommended treatment of maternal
hypothyroidism is with administration of oral LT4. It is strongly
recommended not to use other thyroid preparations such as T3 or
desiccated thyroid. Level A-USPSTF
RECOMMENDATION 11 - The goal of LT4 treatment is to normalize
maternal serum TSH values within the trimester-specific pregnancy
reference range (first trimester, 0.1–2.5 mIU/L; second trimester, 0.2–
3.0 mIU/L; third trimester, 0.3–3.0 mIU/L). Level A-USPSTF

43. • RECOMMENDATION 12 - Women with SCH in pregnancy who are not initially
treated should be monitored for progression to OH with a serum TSH and
FT4 approximately every 4 weeks until 16–20 weeks gestation and at least once
between 26 and 32 weeks gestation. This approach has not been prospectively
studied. Level I-USPSTF
• RECOMMENDATION 13 - Treated hypothyroid patients (receiving LT4) who are
newly pregnant should independently increase their dose of LT4 by ∼25%–30%
upon a missed menstrual cycle or positive home pregnancy test and notify
their caregiver promptly. One means of accomplishing this adjustment is to
increase LT4 from once daily dosing to a total of nine doses per week (29%
increase). Level B-USPSTF
• RECOMMENDATION 14 - There exists great inter- individual variability
regarding the increased amount of T4 (or LT4) necessary to maintain a normal
TSH throughout pregnancy, with some women requiring only 10%–20%
increased dosing, while others may require as much as an 80% increase. The
etiology of maternal hypothyroidism, as well as the preconception level of
TSH, may provide insight into the magnitude of necessary LT4 increase.
Clinicians should seek this information upon assessment of the patient after
pregnancy is confirmed. Level A-USPSTF

44. RECOMMENDATION 15 - Treated hypothyroid patients (receiving LT4) who
are planning pregnancy should have their dose adjusted by their
provider in order to optimize serum TSH values to <2.5 mIU/L
preconception. Lower preconception TSH values (within the
nonpregnant reference range) reduce the risk of TSH elevation during
the first trimester. Level B-USPSTF
RECOMMENDATION 16 - In pregnant patients with treated
hypothyroidism, maternal serum TSH should be monitored
approximately every 4 weeks during the first half of pregnancy
because further LT4 dose adjustments are often required. Level B-
USPSTF
RECOMMENDATION 17 - In pregnant patients with treated
hypothyroidism, maternal TSH should be checked at least once
between 26 and 32 weeks gestation. Level I-USPSTF
RECOMMENDATION 18 - Following delivery, LT4 should be reduced to the
patient's preconception dose. Additional TSH testing should be
performed at approximately 6 weeks postpartum. Level B-USPSTF

45. RECOMMENDATION 19 - In the care of women with adequately
treated Hashimoto's thyroiditis, no other maternal or fetal thyroid
testing is recommended beyond measurement of maternal thyroid
function (such as serial fetal ultrasounds, antenatal testing, and/or
umbilical blood sampling) unless for other pregnancy
circumstances. Level A-USPSTF
RECOMMENDATION 20 - Euthyroid women (not receiving LT4) who
are TAb+ require monitoring for hypothyroidism during pregnancy.
Serum TSH should be evaluated every 4 weeks during the first half
of pregnancy and at least once between 26 and 32 weeks
gestation. Level B-USPSTF
RECOMMENDATION 21 - A single RCT has demonstrated a reduction
in postpartum thyroiditis from selenium therapy. No subsequent
trials have confirmed or refuted these findings. At present,
selenium supplementation is not recommended for TPOAb+
women during pregnancy. Level C-USPSTF

46. CONGENITAL HYPOTHYROIDISM
• Abnormality in the development of thyroid gland (dysgenesis or agenesis)
and defect in the biosynthesis of thyroid hormones
• Prevalence rate 1 in 4000 newborn infants in regions of sufficient daily
iodine intake
• 2:1 incidence in females compared with males
• Causes: Endemic iodine deficiency, genetic mutation, and hemangiomas
• Routine thyroid function screening in neonates is recommended since no
apparent clinical manifestation
• Untreated congenital hypothyroidism results in development of cretinism
• Do not delay diagnosis of congenital hypothyroidism until physical
manifestations are seen
– Mental retardation
– Deafness
– Short stature
– Characteristic facial deformities

47. CONGENITAL HYPOTHYROIDISM:
CLINICAL FEATURES
Roberts CGP et al. Lancet. 2004;363: 793-803.
Infants Children and Adolescents
Hypothermia Growth failure
Poor feeding Markedly delayed bone maturation
Bradycardia
Delayed eruption of permanent
teeth
Jaundice Muscle pseudohypertrophy
Enlarged posterior fontanel Delayed or precocious puberty
Umbilical hernia Pituitary enlargement
Galactorrhoea

48. MANAGEMENT OF CONGENITAL HYPOTHYROIDISM
• Goal: To normalize T4 within 2 weeks and TSH within 1 month
• Assess permanence of congenital hypothyroidism
– If initial thyroid scan shows ectopic/absent gland, congenital
hypothyroidism is permanent
– If initial TSH is <50 mIU/L and there is no increase in TSH after
newborn period, off- therapy period is recommended at 3 years
of age
– If TSH increases during the off-therapy period, consider the
condition as permanent congenital hypothyroidism
• Medications: LT4: 10-15 g/kg by mouth once-daily
• Monitoring: Recheck T4 and TSH
– At 2-4 weeks after initiation of LT4 treatment
– Every 1-2 months in the first 6 months
– Every 3-4 months between 6 months and 3 years of age
– Every 6-12 months from 3 years of age to end of growth
Rose SR and Brown RS. Pediatrics. 2006;117(6):2290-2303.

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